WASPTRAFFICDC · Trafficking of DC in Wiskott Aldrich syndrome
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2007-04-02 → 2009-04-01
- EU contribution
- €167,664
- Participants
- 1
- Scheme
- EIF
Lines connect the coordinator with its partners.
Results in brief
Final Activity Report Summary - WASPTRAFFICDC (Trafficking of DC in Wiskott Aldrich Syndrome)
Wiskott-Aldrich Syndrome (WAS) is caused by gene mutations that result in lack of expression of a specific protein called Wiskott-Aldrich Syndrome protein (WASp). As a result, patients who suffer from this rare X-linked immunodeficiency, do not have a fully functional immune system as all cells of the immune system lack WASp and consequently fail to function properly. An important regulator of immune responses is a particular type of immune cell called dendritic cell (DC). In our research we have been investigated the mechanism how defective function of DCs in WAS contribute to failing of the immune system. We have observed that WAS DC fail to activate T cells, which are important effector immune cells and crucial in establishing effective long-term protection against bacteria and viruses. Our research has investigated the interaction between DC and T cells and we have observed that lack of WASp causes failure to form the signalling structure between DC and T cells, which normally mediates activation of T cells and is responsible for the initiation of a protective immune response. Our research is providing insights into the pathophysiology of WAS and contributes to better understanding of how DCs interact with T cells in general. In particular, our findings highlight the importance of correcting DC function in WAS for therapeutic intervention.
Data: CORDIS, © European Union
Project objective
The spatial and temporal distribution of dendritic cells (DC) is essential for the initiation of specific immunity and tolerance. Patients with Wiskott Aldrich Syndrome (WAS) show loss of WAS protein (WASp) function, resulting in impaired immune cell migration and abnormal splenic architecture. Ongoing studies of the host laboratory suggest that DC migration to inflamed tissue and to draining lymphoid tissue is compromised and accompanied by exaggerated production of pro-inflammatory cytokines, such as IL-1 2 and IL-6 in vitro. We hypothesise that deficient DC migration may impair normal immune cell distribution in lymphoid tissue and influence subsequent immune function.We therefore aim to determine the role of WASp in DC biology and its specific role in DC migration.1. We will study the role of WASp in the distribution of DC subsets and their cytokine expression in response to TLR stimulation.2. We will investigate whether and how WASp regulates the migration and localisation of DC in steady state and in inflammatory conditions.3. We will use two-photon laser microscopy to study the real time migratory behaviour of WASp-/- DC and their interaction with other immune cells.We expect this project to have profound impact on my scientific career and more in general in the field of DC biology. Better understanding of the role of WASp in DC migration and in immune function will provide better insight in the immunological pathogenesis of WAS and may provide important information for design of new therapies.
Original text from CORDIS.
Participants
- UNIVERSITY COLLEGE LONDON · LONDONCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union